A longitudinal cohort study of maternal cardiovascular and biomarker changes in fetal growth restriction and pre-eclampsia

Abstract

Pre eclampsia (PE) and fetal growth restriction (FGR) are perceived as placenta mediated disorders. However, large epidemiological studies has shown that women diagnosed with PE have significantly higher risk of cardiovascular disease in later life. Hence, the pathophysiology of PE and FGR might be more closely linked to the maternal heart than previously thought. Maladaptation to haemodynamic changes in pregnancy could herald the manifestation of PE and FGR. Traditionally, PE is classified into “early”, onset prior to 34 weeks gestation; and “late” onset after 34 weeks. This arbitrary classification was decided because early PE usually co-exist with FGR and therefore clinically distinct from late PE. Women across gestation (24-40 weeks) with PE, FGR,PEFGR and normal outcomes were recruited. At each visit, maternal cardiovascular and arterial function was studied, ultrasound examination performed and serum/urine collected. Those with PE and/or FGR participated in an exercise step test. In PE, there was increased cardiac output (CO) and lower peripheral vascular resistance (PVR). Conversely, pregnancies with FGR, regardless of whether PE co-exists, showed increased PVR, independent of gestational age. Arterial function was abnormal in all pathological cases. Low maternal CO and high maternal PVR are associated with raised impedance in the maternal uterine and fetal umbilical arteries. Metabonomic characterisation and BAFF /PAF immunological marker support the distinction of PE from PEFGR. In conclusion, this study has established distinct cardiovascular haemodynamic and serum profile in normal, PE and FGR pregnancies, irrespective of gestational age. Maternal cardiovascular profile is associated with utero-placental and fetal Doppler changes. These findings have implications on clinical choice of antihypertensives in pregnancy. It also raises the possibility of improving fetal outcomes via manipulation of maternal cardiac function pharmacologically. There were no obvious differences in cardiovascular adaptation neither in relation to exercise nor postnatally between the groups.Open Acces